These results of this study indicate that the C-H bond of the difluoromethyl group of enflurane is not significantly susceptible to metabolic oxidative defluorination. This finding can be used for the rational design of new inhalation anesthetics which will not be appreciably metabolized to fluoride ion. The study also demonstrates an important use of specifically deuterated derivatives for readily determining the major pathways of defluorination of enflurane in various microsomal preparations.